EVENITY (Romosozumab)
Monoclonal antibody for severe postmenopausal osteoporosis – builds new bone and slows bone loss
EVENITY (romosozumab) is a prescription monoclonal antibody used to treat severe osteoporosis in postmenopausal women at high risk of fractures. It works by blocking a protein called sclerostin, which has a unique dual action: it stimulates new bone formation while simultaneously slowing bone breakdown. EVENITY is administered as two subcutaneous injections once monthly for 12 months. It carries a cardiovascular warning and is contraindicated in patients with a history of heart attack or stroke.
Quick Facts
Key Takeaways
- EVENITY is the first and only sclerostin inhibitor approved for osteoporosis, offering a unique dual mechanism that simultaneously builds new bone and reduces bone loss.
- Treatment involves two subcutaneous injections (105 mg each) given once a month for a fixed 12-month course, after which patients transition to another osteoporosis therapy.
- Clinical trials (FRAME and ARCH) demonstrated significant reductions in vertebral, non-vertebral, and hip fractures in postmenopausal women with osteoporosis.
- EVENITY carries a cardiovascular warning: it is contraindicated in patients with a history of heart attack or stroke, and cardiovascular risk factors should be carefully evaluated before prescribing.
- Patients must take calcium and vitamin D supplements throughout treatment to prevent hypocalcemia (low blood calcium levels).
What Is EVENITY and What Is It Used For?
EVENITY contains the active substance romosozumab, a humanized monoclonal antibody (IgG2) designed to help strengthen the skeleton and reduce the risk of bone fractures. It is specifically approved for the treatment of severe osteoporosis in postmenopausal women who have a high risk of experiencing fractures. Osteoporosis is a progressive skeletal disease characterized by reduced bone density and deterioration of bone tissue, leading to increased fragility and susceptibility to fractures, particularly of the spine, hip, and wrist.
Many patients with osteoporosis experience no outward symptoms until a fracture occurs, making the condition often referred to as a "silent disease." According to the International Osteoporosis Foundation (IOF), osteoporosis causes more than 8.9 million fractures annually worldwide, with approximately one in three women over the age of 50 experiencing an osteoporotic fracture in their lifetime. EVENITY was developed to address a significant unmet need for patients with the most severe forms of osteoporosis who are at very high risk of fracture.
How Does EVENITY Work?
EVENITY works through a novel mechanism of action that distinguishes it from all other available osteoporosis treatments. Romosozumab is a monoclonal antibody – a type of protein engineered to recognize and bind to specific target proteins in the body. In this case, EVENITY binds to and blocks a protein called sclerostin.
Sclerostin is a glycoprotein produced primarily by osteocytes (mature bone cells embedded within the bone matrix). Under normal conditions, sclerostin acts as a negative regulator of bone formation by inhibiting the Wnt signaling pathway, which is essential for osteoblast (bone-building cell) activity. By binding to and neutralizing sclerostin, romosozumab achieves a unique dual effect on bone metabolism:
- Stimulates bone formation: Blocking sclerostin activates the Wnt pathway, promoting osteoblast differentiation, proliferation, and function. This leads to the rapid creation of new bone tissue, increasing bone mineral density (BMD) at both trabecular and cortical bone sites.
- Reduces bone resorption: EVENITY simultaneously decreases the activity of osteoclasts (bone-resorbing cells), slowing the breakdown of existing bone. This anti-resorptive effect complements the anabolic bone-building action.
This dual mechanism – simultaneously increasing bone formation and decreasing bone resorption – results in rapid and substantial gains in bone mineral density, particularly at the lumbar spine and total hip. In the pivotal FRAME trial, romosozumab increased lumbar spine BMD by 13.3% and total hip BMD by 6.9% over 12 months, significantly exceeding the gains observed with any other single osteoporosis agent. The net effect is stronger bones and a reduced risk of fractures.
Healthy bones undergo constant remodeling – a balanced cycle of bone resorption (breakdown by osteoclasts) and bone formation (building by osteoblasts). In osteoporosis, this balance shifts toward excessive resorption, resulting in net bone loss. Most current osteoporosis therapies are anti-resorptive (e.g., bisphosphonates, denosumab), meaning they only slow bone loss. EVENITY is unique because it acts on both sides of the equation, actively building new bone while also reducing resorption.
What Should You Know Before Taking EVENITY?
Before starting treatment with EVENITY, your healthcare provider will conduct a thorough medical evaluation to ensure the medication is appropriate for you. There are important contraindications, warnings, and precautions that must be carefully considered. Open communication with your doctor about your full medical history, including all existing conditions and current medications, is essential for safe and effective treatment.
Contraindications
You must not use EVENITY if any of the following apply:
- Allergy to romosozumab or any of the other ingredients in EVENITY (including calcium acetate, glacial acetic acid, sodium hydroxide, sucrose, polysorbat 20, and water for injections).
- Low blood calcium levels (hypocalcemia): Your doctor will check your calcium levels before starting treatment. Hypocalcemia must be corrected before initiating EVENITY.
- History of heart attack (myocardial infarction) or stroke: Clinical data from the ARCH trial showed an increased incidence of cardiovascular events in patients treated with romosozumab compared to alendronate. EVENITY is therefore contraindicated in patients with a history of myocardial infarction or stroke.
Warnings and Precautions
Heart attack and stroke have been reported in patients receiving EVENITY. Seek immediate medical attention if you experience: chest pain or shortness of breath; sudden headache, numbness or weakness in the face, arms, or legs; difficulty speaking; vision changes; or loss of balance. Your doctor will carefully evaluate your cardiovascular risk profile before prescribing EVENITY. Inform your doctor if you have established cardiovascular disease, high blood pressure, high cholesterol, diabetes, smoking history, or kidney problems.
Hypocalcemia (low blood calcium): EVENITY can cause dangerously low blood calcium levels. Tell your doctor immediately if you notice muscle spasms, twitching, or cramps; or numbness or tingling in your fingers, toes, or around your mouth. Your doctor will prescribe calcium and vitamin D supplements before you start and throughout your treatment. Patients with severe kidney impairment, kidney failure, or those on dialysis are at higher risk and require closer monitoring.
Serious allergic reactions: Although rare, serious allergic reactions including angioedema (swelling of the face, mouth, throat, hands, feet, ankles, or lower legs), urticaria (hives), and erythema multiforme (acute skin rashes with round red or pink spots with blisters or crusts) have been reported. Seek immediate medical attention if you experience swelling, severe skin rashes, or difficulty swallowing or breathing after receiving EVENITY.
Osteonecrosis of the jaw (ONJ): This rare but serious condition involves damage to the jawbone and has been reported in patients receiving EVENITY, including after treatment has ended. Before starting treatment, inform your doctor if you have dental problems, poor oral health, gum disease, a planned tooth extraction, do not visit a dentist regularly, are a smoker, have previously been treated with bisphosphonates, take corticosteroids, or have cancer. During treatment, maintain good oral hygiene, attend regular dental check-ups, and inform both your doctor and dentist about your EVENITY treatment before any dental procedures.
Atypical femoral fractures: In rare cases, patients taking EVENITY have experienced unusual fractures of the thigh bone (femur) with little or no trauma. These fractures are often preceded by warning signs of pain in the thigh or groin area for several weeks before the fracture occurs. Tell your doctor if you develop new or unusual pain in your hip, groin, or thigh.
Pregnancy and Breastfeeding
EVENITY is indicated exclusively for the treatment of postmenopausal women. It should not be used by women of childbearing potential, during pregnancy, or while breastfeeding. It is not known whether romosozumab can harm an unborn child or pass into breast milk. If you have any questions about this, consult your doctor.
Children and Adolescents
EVENITY has not been studied in children and adolescents and is not approved for use in patients under 18 years of age. The safety and efficacy of romosozumab in pediatric populations have not been established.
Driving and Operating Machinery
EVENITY is expected to have no or negligible effect on the ability to drive and use machines. No studies on the effect on driving ability have been performed, but based on the pharmacological properties of romosozumab, no impairment is expected.
How Does EVENITY Interact with Other Drugs?
No formal drug interaction studies have been conducted with romosozumab. As a monoclonal antibody, EVENITY is not metabolized by cytochrome P450 enzymes and is not expected to interact with most conventional medications through pharmacokinetic mechanisms. However, there are important clinical considerations regarding concurrent medications and conditions that your healthcare provider should be aware of.
Always tell your doctor or pharmacist about all medications you are currently taking, have recently taken, or might take. This includes prescription medicines, over-the-counter drugs, vitamins, and herbal supplements. While EVENITY does not have traditional drug-drug interactions, certain medications may influence the safety profile or clinical context of treatment.
| Medication | Consideration | Clinical Recommendation |
|---|---|---|
| Calcium supplements | Required to prevent hypocalcemia during treatment | Take as directed by your doctor throughout EVENITY treatment |
| Vitamin D supplements | Required to support calcium absorption and prevent hypocalcemia | Take as directed by your doctor; levels may be checked before starting |
| Bisphosphonates (e.g., alendronate, zoledronic acid) | Prior use may increase risk of ONJ; sequential use after EVENITY is standard of care | Inform your doctor of any previous bisphosphonate use; transition to antiresorptive after completing EVENITY |
| Denosumab (Prolia) | Another anti-osteoporosis biologic; sequential use is an option after EVENITY | Discuss sequencing strategy with your doctor |
| Corticosteroids (e.g., prednisolone, dexamethasone) | May increase risk of osteonecrosis of the jaw; can worsen bone loss | Inform your doctor; additional monitoring may be needed |
| Other monoclonal antibodies | No known pharmacokinetic interactions; clinical data on concurrent use is limited | Inform your doctor about all biologic medications you are taking |
It is important to note that after completing the 12-month course of EVENITY, your doctor will transition you to another osteoporosis medication (typically a bisphosphonate or denosumab) to maintain the bone density gains achieved. This sequential treatment approach is a critical part of the overall treatment strategy and should be discussed with your healthcare provider before starting EVENITY.
What Is the Correct Dosage of EVENITY?
EVENITY treatment should be initiated and supervised by a specialist physician experienced in the management of osteoporosis. The medication must be administered by a person who has received appropriate training in subcutaneous injection technique. Always use EVENITY exactly as your doctor has instructed.
Adults (Postmenopausal Women)
Standard Dosing Regimen
Dose: 210 mg once monthly
Administration: Two pre-filled pens of 105 mg each (total = 210 mg), given as two separate subcutaneous injections
Duration: 12 months (12 doses total)
Route: Subcutaneous injection into the abdomen, thigh, or outer upper arm (upper arm only if administered by another person)
Each pre-filled pen contains 105 mg of romosozumab in 1.17 mL of solution (90 mg/mL). Since the full dose is 210 mg, two pre-filled pens must be used for each monthly dose. The second injection must be given immediately after the first, but at a different injection site. If the same injection area is used (e.g., both in the abdomen), a different spot within that area must be selected.
EVENITY should not be injected into areas where the skin is tender, bruised, red, or hard. Before injecting, allow the pre-filled pens to reach room temperature (up to 25°C) for at least 30 minutes after removing from the refrigerator. Do not warm the pens by any other method, and do not shake them.
Injection Technique
The EVENITY pre-filled pen is designed for ease of use. After removing the white cap, place the yellow safety guard on the cleaned skin at a 90-degree angle and press firmly. You will hear or feel a click when the injection begins. Continue pressing for approximately 15 seconds until the viewing window turns completely yellow, indicating the full dose has been delivered. If the window does not turn completely yellow, inform your doctor as the full dose may not have been delivered.
Children and Adolescents
Pediatric Use
Not approved for use in patients under 18 years of age. The safety and efficacy of EVENITY in children and adolescents have not been established.
Elderly Patients
Elderly Dosing
No dose adjustment is required for elderly patients. EVENITY has been studied in women up to 89 years of age in clinical trials. However, cardiovascular risk should be carefully evaluated in older patients, as the incidence of cardiovascular risk factors increases with age.
Renal and Hepatic Impairment
Special Populations
Renal impairment: No dose adjustment is needed. However, patients with severe kidney impairment or on dialysis are at increased risk of hypocalcemia and should be monitored more closely. Calcium levels should be checked regularly.
Hepatic impairment: No clinical studies have been conducted in patients with hepatic impairment. As a monoclonal antibody, romosozumab is expected to be eliminated by intracellular catabolism, not hepatic metabolism. No dose adjustment is anticipated.
Missed Dose
If you miss a dose of EVENITY, contact your doctor as soon as possible to schedule your next injection. After a missed dose, the subsequent dose should not be given sooner than one month after the last administered dose. Resume the regular monthly schedule from the date of the rescheduled injection.
Overdose
If you accidentally use more EVENITY than prescribed, contact your doctor or pharmacist immediately. There is limited clinical experience with overdose of romosozumab. In clinical studies, no dose-limiting toxicities were identified with doses up to 210 mg administered subcutaneously. In the event of overdose, the patient should be monitored for signs of hypocalcemia, and supportive care should be provided as clinically indicated.
After Completing EVENITY Treatment
After the 12-month course of EVENITY is completed, it is essential to transition to another osteoporosis therapy to maintain the bone density gains. The bone-forming effect of romosozumab diminishes over time, and without continuation therapy, bone density may decline. Discuss your follow-up treatment plan with your doctor before completing EVENITY. Common sequential therapies include bisphosphonates (such as alendronate or zoledronic acid) or denosumab.
What Are the Side Effects of EVENITY?
Like all medicines, EVENITY can cause side effects, although not everybody experiences them. Most side effects are mild to moderate and resolve without treatment. However, some side effects can be serious and require immediate medical attention. It is important to be aware of the warning signs of serious adverse events so that you can seek prompt medical care if needed.
Contact emergency services or go to your nearest emergency department immediately if you experience symptoms of a heart attack or stroke (chest pain, shortness of breath, sudden severe headache, numbness or weakness in the face, arms, or legs, difficulty speaking, vision changes, or balance problems). Also seek emergency care for signs of a serious allergic reaction (swelling of face, mouth, throat, hands or feet, severe skin rash, or difficulty swallowing or breathing).
Very Common
- Nasopharyngitis (common cold)
- Arthralgia (joint pain)
Common
- Skin rash or dermatitis
- Headache
- Sinusitis (sinus inflammation)
- Neck pain
- Muscle spasms
- Injection site reactions (redness, pain, or swelling)
Uncommon
- Urticaria (hives)
- Cataract
- Hypocalcemia (low blood calcium)
- Myocardial infarction (heart attack)
- Stroke (cerebrovascular accident)
Rare
- Angioedema (severe swelling)
- Erythema multiforme (severe skin reaction)
- Osteonecrosis of the jaw
- Atypical femoral fracture
Cardiovascular Events in Detail
In the ARCH clinical trial, which compared romosozumab with alendronate, a higher rate of adjudicated major adverse cardiac events (MACE) was observed in the romosozumab group during the first 12 months of treatment. Specifically, cardiovascular death, myocardial infarction, and stroke occurred in 2.5% of patients receiving romosozumab compared to 1.9% in the alendronate group. This finding led regulatory agencies including the EMA and FDA to include a boxed warning (in the US) and contraindication for patients with prior cardiovascular events.
It is important to note that the FRAME trial, which compared romosozumab with placebo, did not show a significant imbalance in cardiovascular events. The cardiovascular signal was primarily observed in the ARCH trial population, which included patients with higher baseline cardiovascular risk. Nevertheless, healthcare providers should carefully weigh the cardiovascular risks and benefits before prescribing EVENITY, particularly in patients with established cardiovascular disease or multiple risk factors.
Injection Site Reactions
Injection site reactions are common and typically mild. These may include redness, pain, swelling, or itching at the site of injection. These reactions usually resolve within a few days without treatment. Rotating injection sites between the abdomen, thighs, and upper arms can help minimize injection site reactions over the course of treatment.
Reporting Side Effects
If you experience any side effects, including those not listed above, talk to your doctor, pharmacist, or nurse. You can also report side effects directly to your national medicines regulatory authority. By reporting side effects, you help provide more information on the safety of EVENITY and contribute to the ongoing monitoring of the medicine's benefit-risk balance.
How Should You Store EVENITY?
Proper storage of EVENITY is essential to maintain the medication's effectiveness and safety. The pre-filled pens contain a biologic protein (monoclonal antibody) that is sensitive to temperature extremes and light exposure. Follow these storage instructions carefully:
- Refrigerate: Store in the refrigerator at 2°C to 8°C (36°F to 46°F).
- Do not freeze: If the product has been frozen, do not use it. Discard it safely.
- Room temperature storage: Once removed from the refrigerator, EVENITY can be stored at room temperature (up to 25°C / 77°F) for a maximum of 30 days. Once at room temperature, do not return it to the refrigerator.
- Protect from light: Keep the pre-filled pens in the original outer carton until ready to use.
- Keep out of reach of children.
- Check expiration date: Do not use EVENITY after the expiry date printed on the label and carton (EXP). The expiry date refers to the last day of that month.
Before use, visually inspect the solution. EVENITY should appear as a clear to opalescent, colorless to light yellow liquid. Do not use if the solution is discolored, cloudy, or contains flakes or particles. Small air bubbles may be present in the solution – this is normal and does not affect safety or efficacy.
Dispose of used pre-filled pens in a sharps disposal container immediately after use. Do not dispose of pens in household waste. Do not recycle used pens. Ask your pharmacist how to properly dispose of medicines you no longer use. These measures help protect the environment and prevent accidental needle-stick injuries.
What Does EVENITY Contain?
Understanding the composition of your medication can be important, particularly if you have known allergies to specific excipients. EVENITY is supplied as a clear to opalescent, colorless to light yellow solution for injection in a single-use pre-filled pen. The syringe inside the pen is made of plastic with a stainless steel needle.
| Component | Details | Function |
|---|---|---|
| Romosozumab | 105 mg per 1.17 mL (90 mg/mL) | Active ingredient – anti-sclerostin monoclonal antibody |
| Calcium acetate | Excipient | Buffer – maintains pH stability |
| Glacial acetic acid | Excipient | Buffer component |
| Sodium hydroxide | For pH adjustment | pH adjuster |
| Sucrose | Excipient | Stabilizer – protects the protein structure |
| Polysorbat 20 | 0.070 mg per pen | Surfactant – prevents protein aggregation |
| Water for injections | To volume | Solvent |
Sodium content: This medicine contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially sodium-free.
Polysorbat 20: This excipient may cause allergic reactions in sensitive individuals. Inform your doctor if you have any known allergies to polysorbates.
Packaging
EVENITY is available in packs of 2 pre-filled pens (one month's supply) and multipacks of 6 pre-filled pens (3 packs of 2, representing a three-month supply). Not all pack sizes may be marketed in all countries.
The marketing authorization holder is UCB Pharma S.A. (Brussels, Belgium), and the manufacturer is Amgen Europe B.V. (Breda, Netherlands). EVENITY is approved for use in the European Union, the United States, Japan, and numerous other countries worldwide.
Frequently Asked Questions About EVENITY
EVENITY (romosozumab) is used to treat severe osteoporosis in postmenopausal women who are at high risk of bone fractures. It is a monoclonal antibody that works by blocking sclerostin, a protein that inhibits bone formation. By inhibiting sclerostin, EVENITY has a unique dual mechanism of action: it simultaneously builds new bone tissue and slows the breakdown of existing bone. This results in rapid and substantial increases in bone mineral density, significantly reducing the risk of vertebral, non-vertebral, and hip fractures.
EVENITY is given as two subcutaneous injections of 105 mg each (total dose 210 mg) once a month for 12 months. The injections are given in the abdomen, thigh, or outer upper arm (if administered by someone else). Both injections should be given immediately after one another but at different injection sites. The pens should be allowed to reach room temperature for at least 30 minutes before use. Treatment should be administered by a trained healthcare professional or a patient who has received proper injection training.
Serious side effects include an increased risk of heart attack and stroke (uncommon, up to 1 in 100 people), serious allergic reactions including angioedema and erythema multiforme (rare, up to 1 in 1,000), hypocalcemia (low blood calcium), osteonecrosis of the jaw (rare), and atypical femoral fractures (rare). Seek immediate medical attention if you experience chest pain, shortness of breath, sudden headache, numbness or weakness, difficulty speaking, vision changes, or signs of severe allergic reaction.
EVENITY is currently approved specifically for the treatment of severe osteoporosis in postmenopausal women at high risk of fracture. While romosozumab has been studied in men with osteoporosis and showed positive results on bone mineral density, the primary approved indication remains postmenopausal osteoporosis. In some countries, regulatory authorities may have granted or be considering expanded indications. Consult your doctor to discuss whether EVENITY may be appropriate for your specific situation based on the latest prescribing guidelines in your country.
After completing the 12-month course, your doctor will transition you to another osteoporosis treatment, typically an antiresorptive medication such as a bisphosphonate (e.g., alendronate or zoledronic acid) or denosumab. This is essential because the bone-forming effect of EVENITY diminishes after 12 months, and continued treatment is needed to maintain the gains in bone mineral density. In the FRAME trial extension, patients who transitioned from romosozumab to denosumab continued to gain bone density over the following 12 months. Stopping all osteoporosis treatment after EVENITY can lead to rapid bone loss.
Yes, EVENITY should be stored in the refrigerator at 2°C to 8°C. However, once removed from the refrigerator, it can be kept at room temperature (up to 25°C) for up to 30 days. After this period, if not used, it must be discarded. Do not freeze EVENITY, and keep it in the original carton to protect from light. Before injection, allow the pre-filled pens to warm to room temperature for at least 30 minutes for a more comfortable injection.
References
- European Medicines Agency (EMA). EVENITY (romosozumab) – Summary of Product Characteristics. Last updated 2024. Available from: EMA EPAR: EVENITY.
- Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016;375(16):1532-1543. doi:10.1056/NEJMoa1607948.
- Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis (ARCH trial). N Engl J Med. 2017;377(15):1417-1427. doi:10.1056/NEJMoa1708322.
- Lewiecki EM, Blicharski T, Goemaere S, et al. A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis (BRIDGE study). J Clin Endocrinol Metab. 2018;103(9):3183-3193. doi:10.1210/jc.2017-02163.
- International Osteoporosis Foundation (IOF). Osteoporosis – Facts and Statistics. Available from: www.osteoporosis.foundation.
- U.S. Food and Drug Administration (FDA). EVENITY Prescribing Information. Available from: FDA Label.
- Shoback D, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society Guideline Update. J Clin Endocrinol Metab. 2020;105(3):587-594.
- Eastell R, Rosen CJ, Black DM, et al. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Updated Clinical Practice Guideline From the Endocrine Society. J Clin Endocrinol Metab. 2023;108(4):820-832.
Medical Editorial Team
Written by: iMedic Medical Editorial Team
Specialists in endocrinology, rheumatology, and clinical pharmacology with extensive experience in osteoporosis management and bone metabolism.
Reviewed by: iMedic Medical Review Board
Independent panel of board-certified physicians who review all content according to international clinical guidelines and evidence-based medicine standards (GRADE framework).
Evidence Standard: All medical claims in this article are supported by Level 1A evidence from randomized controlled trials and systematic reviews. Sources include the EMA Summary of Product Characteristics, FDA prescribing information, and peer-reviewed publications in the New England Journal of Medicine and Journal of Clinical Endocrinology & Metabolism.
Conflict of Interest: The iMedic editorial team has no financial relationships with pharmaceutical companies. This content is independently produced with no commercial funding or pharmaceutical sponsorship.